Many secreted proteins, for example, cytokines and cytokine receptors, play a vital role in the regulation of cell growth, cell differentiation, and a variety of specific cellular responses. A number of medically useful proteins, including erythropoietin, granulocyte-macrophage colony stimulating factor, human growth hormone, and various interleukins, are secreted proteins. Thus, an important goal in the design and development of new therapies is the identification and characterization of secreted and transmembrane proteins and the genes which encode them.
Many secreted proteins are receptors which bind a ligand and transduce an intracellular signal, leading to a variety of cellular responses. The identification and characterization of such a receptor enables one to identify both the ligands which bind to the receptor and the intracellular molecules and signal transduction pathways associated with the receptor, permitting one to identify or design modulators of receptor activity, e.g., receptor agonists or antagonists and modulators of signal transduction.
The present invention is based, at least in part, on the discovery of cDNA molecules which encode the TANGO 253, 257 and 281 proteins and the INTERCEPT 258 protein, all of which are either wholly secreted or transmembrane proteins.
The TANGO 253 proteins are C1q domain-containing polypeptides that exhibit homologue to a human adipocyte complement-related protein precursor.
The TANGO 257 proteins are homologous to the human extracellular molecule olfactomedin, a molecule important in the maintenance, growth and differentiation of chemosensory cilia of olfactory neurons.
The INTERCEPT 258 proteins are Ig domain-containing polypeptides that exhibit homology to an antigen (A33) expressed in colonic and small bowel epithelium, a protein that may represent a cancer cell marker.
The TANGO 281 proteins represent proteins downregulated in megakaryocytes that fail to express the gata-1 transcription factor (a factor critical for blood cell formation) and can, therefore, represent direct or indirect gata-1 targets.
The TANGO 253, TANGO 257, INTERCEPT 258 and TANGO 281 proteins, fragments, derivatives, and variants thereof are collectively referred to herein as xe2x80x9cpolypeptides of the inventionxe2x80x9d or xe2x80x9cproteins of the invention.xe2x80x9d Nucleic acid molecules encoding the polypeptides or proteins of the invention are collectively referred to as xe2x80x9cnucleic acids of the invention.xe2x80x9d
The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes. Accordingly, in one aspect, this invention provides isolated nucleic acid molecules encoding a polypeptide of the invention or a biologically active portion thereof The present invention also provides nucleic acid molecules which are suitable for use as primers or hybridization probes for the detection of nucleic acids encoding a polypeptide of the invention.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, the nucleotide sequence of the cDNA insert of an EpT253 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:8, SEQ ID NO:9, the nucleotide sequence of the cDNA insert of an EpTm253 clone deposited with ATCC as Accession Number 207215, or a complement thereof.
The invention features nucleic acid molecules which are at least 95% or 98% identical to the nucleotide sequence of SEQ ID NO:15, the nucleotide sequence of the cDNA insert of an EpT257 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 95% or 98% identical to the nucleotide sequence of SEQ ID NO:21, the nucleotide sequence of the cDNA insert of an EpTm257 clone deposited with ATCC as Accession Number 207217, or a complement thereof.
The invention features nucleic acid molecules which are at least 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:26, SEQ ID NO:27, the nucleotide sequence of the cDNA insert of an EpT258 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:37, SEQ ID NO:38, the nucleotide sequence of the cDNA insert of an EpTm258 clone deposited with ATCC as Accession Number 207221, or a complement thereof.
The invention features nucleic acid molecules which are at least 30%, 35%, 40%, 35 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:46, the nucleotide sequence of the cDNA insert of an EpT281 clone deposited with ATCC as Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which are at least 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the nucleotide sequence of SEQ ID NO:56, the nucleotide sequence of the cDNA insert of an EpmT281 clone deposited with ATCC as patent deposit Number PTA-224, or a complement thereof.
The invention features nucleic acid molecules of at least 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 1000, 1100, 1200 or 1300 nucleotides of the nucleotide sequence of SEQ ID NO:1, the nucleotide sequence of an EpT253 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700 or 720 nucleotides of the nucleotide sequence of SEQ ID NO:2, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 540, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200 or 1250 nucleotides of the nucleotide sequence of SEQ ID NO:8 the nucleotide sequence of an EpTm253 cDNa of ATCC Accession Number 207215, or a complement thereof.
The invention features nucleic acid molecules of at least 310, 350, 400, 450, 500, 550, 600, 650 or 700 nucleotides of the nucleotide sequence of SEQ ID NO:9, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 1800 nucleotides of the nucleotide sequence of SEQ ID NO:15 or its complement.
The invention features nucleic acid molecules which include a fragment of at least 1150 or 1200 nucleotides of the nucleotide sequence of SEQ ID NO:16, or its complement.
The invention features nucleic acid molecules which include a fragment of at least 1100, 1200, 1300, 1400, 1500, 1600 or 1700 nucleotides of the nucleotide sequence of SEQ ID NO:21 the nucleotide sequence of an EpTm257 cDNA of ATCC Accession Number 207217, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 1150 or 1200 nucleotides of the nucleotide sequence of SEQ ID NO:22, or its complement.
The invention features nucleic acid molecules which include a fragment of at least 420, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:26 the nucleotide sequence of an EpT258 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:27, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 675, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:37 the nucleotide sequence of an EpTm258 cDNA of ATCC Accession Number 207221, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:38, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides of the nucleotide sequence of SEQ ID NO:46 the nucleotide sequence of an EpT281 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 200, 300, 400, 500, 600, 700 or 750 nucleotides of the nucleotide sequence of SEQ ID NO:47, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 550, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800 or 1850 nucleotides of the nucleotide sequence of SEQ ID NO:56 the nucleotide sequence of an EpTm281 cDNA of ATCC patent deposit Number PTA-224, or a complement thereof.
The invention features nucleic acid molecules which include a fragment of at least 50, 100, 200, 300, 400, 500, 600 or 700 nucleotides of the nucleotide sequence of SEQ ID NO:57, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:3, the amino acid sequence encoded by an EpT253 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 95%, or 98% identical to the amino acid sequence of SEQ ID NO:10, the amino acid sequence encoded by an EpTm253 cDNA of ATCC Accession Number 207115, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 88%, 90%, 95% or 98% identical to the amino acid sequence of SEQ ID NO:17, the amino acid sequence encoded by an EpT257 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 88%, 90%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:23, the amino acid sequence encoded by an EpTm257 cDNA of ATCC Accession Number 207117, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:28, the amino acid sequence encoded by an EpT258 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:39, the amino acid sequence encoded by an EpTm258 cDNA of ATCC Accession Number 207221, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:48, the amino acid sequence encoded by an EpT281 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:58, the amino acid sequence encoded by an EpTm281 of ATCC patent deposit Number PTA-224, or a complement thereof.
The invention also features nucleic acid molecules which include a nucleotide sequence encoding a protein having an amino acid sequence that is at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:3, 10, 17, 23, 28, 39, 48, or 58, the amino acid sequence encoded by EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281, EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, or Accession Number 207221, patent deposit Number PTA-224, or a complement thereof, wherein the protein encoded by the nucleotide sequence also exhibits at least one structural and/or functional feature of a polypeptide of the invention.
In preferred embodiments, the nucleic acid molecules have the nucleotide sequence of SEQ ID NO:1, 2, 8, 9, 15, 16, 21, 22, 26, 27, 37, 38, 46, 47, 56, 57, or the nucleotide sequence of the cDNA clones of ATCC Accession Number 207222, 207215, 207217, 207221 or 207222.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:3, or a fragment including at least 10, 15, 20, 25, 30, 50, 75, 100, 125, 150, 175, 200 or 225 contiguous amino acids of SEQ ID NO:3, or the amino acid sequence encoded by an EpT253 cDNA of ATCC Accession Number 207222.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:17, or a fragment including at least 10, 15, 20, 25, 30, 50, 75, 100, 125, 150, 175, 200 or 225 contiguous amino acids of SEQ ID NO:10, or the amino acid sequence encoded by an EpTm253 cDNA of ATCC Accession Number 207215.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:10, or a fragment including at least 360, 370, 380, 390 or 400 contiguous amino acids of SEQ ID NO:17, or the amino acid sequence encoded by an EpT257 cDNA of ATCC Accession Number 207222.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:23, or a fragment including at least 360, 370, 380, 390 or 400 contiguous amino acids of SEQ ID NO:23, or the amino acid sequence encoded by an EpTm257 cDNA of ATCC Accession Number 207217.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:3, or a fragment including at least 15, 25, 30, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, or 350 contiguous amino acids of SEQ ID NO:28, or the amino acid sequence encoded by an EpT258 cDNA of ATCC Accession Number 207222.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:39, or a fragment including at least 160, 175, 200, 225, 250, 275, 300, 350 or 375 contiguous amino acids of SEQ ID NO:39, or the amino acid sequence encoded by an EpT258 cDNA of ATCC Accession Number 207221.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:48, or a fragment including at least 15, 25, 30, 50, 75, 100, 125, 150, 175, 200, 225, 235 or 240 contiguous amino acids of SEQ ID NO:48, or the amino acid sequence encoded by an EpT281 cDNA of ATCC Accession Number 207222.
Also within the invention are nucleic acid molecules which encode a fragment of a polypeptide having the amino acid sequence of SEQ ID NO:58, or a fragment including at least 15, 25, 30, 50, 75, 100, 125, 150, 175 or 200 contiguous amino acids of SEQ ID NO:58, or the amino acid sequence encoded by an EpTm281 cDNA of ATCC patent deposit Number PTA-224.
The invention also features nucleic acid molecules which encode a polypeptide fragment of at least 15, 25, 30, 50, 75, 100, 125, 150, 175, 200 or more contiguous amino acids of SEQ ID NO:3, 10, 17, 23, 28, 39, 48 or 58, or the amino acid sequence encoded by EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281 or EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, Accession Number 207221 or patent deposit Number PTA-224, wherein the fragment also exhibits at least one structural and/or functional feature of a polypeptide of the invention.
The invention includes nucleic acid molecules which encode a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:3, 10, 17, 23, 28, 39, 48, 58 or the amino acid sequence encoded by a cDNA of ATCC Accession Numbers 207222, 207215, 207217 or 207221, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule consisting of a nucleic acid sequence encoding SEQ ID NO:3, 10, 28, 39, 48, 58, or the amino acid sequence encoded by a cDNA of ATCC Accession Number 207222, 207215, 207217, 207221 or patent deposit Number PTA-224, a complement thereof under stringent conditions.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 40%, preferably 45%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:3, or the amino acid sequence encoded by an EpT253 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 40%, preferably 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:10, or the amino acid sequence encoded by an EpTm253 cDNA of ATCC Accession Number 207215.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least 88%, 90%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:17, or the amino acid sequence encoded by an EpT257 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least 88%; 90%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:23, or the amino acid sequence encoded by an EpTm257 cDNA of ATCC Accession Number 207217.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 30%, preferably 35%, 45%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:28, or the amino acid sequence encoded by an EpT258 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:39, or the amino acid sequence encoded by an EpTm258 cDNA of ATCC Accession Number 207221.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 30%, preferably 35%, 45%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:48, or the amino acid sequence encoded by an EpT281 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins having an amino acid sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95%, or 98% identical to the amino acid sequence of SEQ ID NO:58, or the amino acid sequence encoded by an EpTm28 1 cDNA of ATCC patent deposit Number PTA-224.
The invention also features isolated polypeptides or proteins having an amino acid sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 65%, 75%, 85%, 95% or 98% identical to the amino acid sequence of SEQ ID NO:3, 10, 17, 23, 28, 39, 48 or 58, or the amino acid sequence encoded by EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281 or EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, Accession Number 207221, patent deposit Number PTA-224, wherein the protein or polypeptides also exhibit at least one structural and/or functional feature of a polypeptide of the invention.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95% or 98% identical the nucleic acid sequence encoding SEQ ID NO:3, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:1 or 2, a complement thereof, or the non-coding strand of an EpT253 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95% or 98% identical the nucleic acid sequence encoding SEQ ID NO:10, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:8 or 9, a complement thereof, or the non-coding strand of an EpTm253 cDNA of ATCC Accession Number 207215.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 45%, 50%, 55%, 60%, 65%, 75%, 85%, or 95% identical to the nucleic acid sequence encoding SEQ ID NO:28, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:26 or 27, a complement thereof, or the non-coding strand of an EpT258 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 45%, 50%, 55%, 60%, 65%, 75%, 85%, or 95% identical to the nucleic acid sequence encoding SEQ ID NO:39, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:37 or 38, a complement thereof, or the non-coding strand of an EpTm258 cDNA of ATCC Accession Number 207221.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, or 95% identical to the nucleic acid sequence encoding SEQ ID NO:48, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:46 or 47, a complement thereof, or the non-coding strand of an EpT281 cDNA of ATCC Accession Number 207222.
Also within the invention are isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, or 95% identical to the nucleic acid sequence encoding SEQ ID NO:58, and isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:56 or 57, a complement thereof, or the non-coding strand of an EpTm281 cDNA of ATCC patent deposit Number PTA-224.
The invention also features isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence that is at least about 30%, preferably 35%, 40%, 45%, 50%, 55%, 60%, 65%, 75%, 85%, 95% or 98% identical to a nucleic acid sequence encoding SEQ ID NO:3, 10, 17, 23, 28, 39, 48 or 58, isolated polypeptides or proteins which are encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:1, 2, 8, 9, 15, 16, 21, 22, 26, 27, 37, 38, 46, 47, 56 or 57, a complement thereof, or the non-coding strand of EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281, EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, Accession Number 207221, patent deposit Number PTA-224, wherein polypeptides or proteins also exhibit at least one structural and/or functional feature of a polypeptide of the invention.
Also within the invention are polypeptides which are naturally occurring allelic variants of a polypeptide that includes the amino acid sequence of SEQ ID NO:3, 10, 17, 23, 28, 39, 48, 58 or the amino acid sequence encoded by a cDNA of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217 Accession Number 207221, or patent deposit Number PTA-224 wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule having the sequence of SEQ ID NO:1, 2, 8, 9, 15, 16, 21, 22, 26, 27, 37, 38, 46, 47, 56, 57 or a complement thereof under stringent conditions.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:1 or 2, or an EpT253 cDNA of ATCC Accession Number 207222, or a complement thereof. In other embodiments, the nucleic acid molecules are at least 450, 500, 550, 600, 650, 700, 750, 800, 1000, 1100, 1200 or 1300 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1 or 2, an EpT253 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:8 or SEQ ID NO:9, an EpTm253 cDNA of ATCC Accession Number 207215, or a complement thereof. In other embodiments, the nucleic acid molecules are at least 540, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100, 1159, 1200, or 1250 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:8 or SEQ ID NO:9, an EpTm253 cDNA of ATCC Accession Number 207215, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:15 or SEQ ID NO:16, an EpT257 cDNA of ATCC Accession Number 207222, or a complement thereof and encode a polypeptide comprising the amino acid sequence of SEQ ID NO:17, or encode a polypeptide comprising at least 360, 370, 380, 390 or 400 contiguous amino acids or SEQ ID NO:17.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:21 or SEQ ID NO:22, an EpTm257 cDNA of ATCC Accession Number 207217, or a complement thereof, and encode a polypeptide comprising the amino acid sequence of SEQ ID NO:23, or a polypeptide comprising at least 360, 370, 380, 390, or 400 contiguous amino acids of SEQ ID NO:23.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:26 or SEQ ID NO:27, an EpT258 cDNA of ATCC Accession Number 207222, or a complement thereof. In other embodiments, the nucleic acid molecules are at least 550, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:26 or SEQ ID NO:27, an EpT258 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:37 or SEQ ID NO:38, an EpTm258 cDNA of ATCC Accession Number 207221, or a complement thereof. In other embodiments, the nucleic acid molecules are at least 650, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800, nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:37 or SEQ ID NO:38, an EpTm258 cDNA of ATCC Accession Number 207221, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:46 or 47, an EpTm281 cDNA of ATCC Accession Number 207222, or a complement thereof. In other embodiments, the nucleic acid molecules are at least 710, 750, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700 or 1800 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:46 or SEQ ID NO:47, an EpT281 cDNA of ATCC Accession Number 207222, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:56 or 57, an EpTm281 cDNA of ATCC patent deposit Number PTA-244, or a complement thereof In other embodiments, the nucleic acid molecules are at least 580, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800 or 1850 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:56 or SEQ ID NO:57, an EpTm281 cDNA of ATCC patent deposit Number PTA-224, or a complement thereof.
The invention also features nucleic acid molecules that hybridize under stringent conditions to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:1, 2, 8, 9, 15, 16, 21, 22, 26, 27, 37, 38, 46, 47, 56 or 57, or a nucleotide sequence of EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281 or EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, Accession Number 207221, patent deposit Number PTA-224, or complement thereof, wherein such nucleic acid molecules encode polypeptides or proteins that exhibit at least one structural and/or functional feature of a polypeptide of the invention.
The invention also features nucleic acid molecules at least 15, preferably 50, 75, 100, 150, 200, 250, 300, 350, 400, 500, 600, 700, 800, 1000, 1100 or 1200 nucleotides in length and hybridize under stringent conditions to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, 2, 8, 9, 15, 16, 21, 22, 26, 27, 37, 38, 46, 47, 56 or 57, or a nucleotide sequence of EpT253, EpTm253, EpT257, EpTm257, EpT258, EpTm258, EpT281 or EpTm281 of ATCC Accession Number 207222, Accession Number 207215, Accession Number 207217, Accession Number 207221, patent deposit Number PTA-224, or a complement thereof, wherein such nucleic acid molecules encode polypeptides or proteins that exhibit at least one structural and/or functional feature of a polypeptide of the invention.
In one embodiment, the invention provides an isolated nucleic acid molecule which is antisense to the coding strand of a nucleic acid of the invention.
Another aspect of the invention provides vectors, e.g., recombinant expression vectors, comprising a nucleic acid molecule of the invention. In another embodiment, the invention provides host cells containing such a vector or engineered to contain and/or express a nucleic acid molecule of the invention. The invention also provides methods for producing a polypeptide of the invention by culturing, in a suitable medium, a host cell of the invention such that a polypeptide of the invention is produced.
Another aspect of this invention features isolated or recombinant proteins and polypeptides of the invention. Preferred proteins and polypeptides possess at least one biological activity possessed by the corresponding naturally-occurring human polypeptide. An activity, a biological activity, or a functional activity of a polypeptide or nucleic acid of the invention refers to an activity exerted by a protein, polypeptide or nucleic acid molecule of the invention on a responsive cell as determined in vivo or in vitro, according to standard techniques. Such activities can be a direct activity, such as an association with or an enzymatic activity on a second protein, or an indirect activity, such as a cellular signaling activity mediated by interaction of the protein with a second protein.
For TANGO 253, biological activities include, e.g., (1) the ability to modulate (this term, as used herein, includes, but is not limited to, xe2x80x9cstabilizexe2x80x9d, promote, inhibit or disrupt, protein-protein interactions (e.g., homophilic and/or heterophilic), and protein-ligand interactions, e.g., in receptor-ligand recognition; (2) ability to modulate cell-cell interactions and/or cell-extracellular matrix interactions; (3) the ability to modulate the host immune response, e.g., by modulating one or more elements in the serum complement cascade; (4) the ability to modulate the proliferation, differentiation and/or activity of cells that form blood vessels and coronary tissue (e.g., coronary smooth muscle cells and/or blood vessel endothelial cells); (5) the ability to modulate intracellular signaling cascades (e.g., signal transduction cascades); and (6) the ability to modulate adipocyte function.
For TANGO 257, biological activities include, e.g., (1) ability to modulate development, differentiation, proliferation and/or activity of neuronal cells, e.g., olfactory neurons (2) ability to modulate development, differentiation, proliferation and/or activity of pulmonary system cells, e.g., lung cell types; (3) ability to modulate cell-cell interactions and/or cell-extracellular matrix interactions, e.g., neuronal cell-extracellular matrix interactions; (4) ability to modulate cell proliferation, e.g., abnormal cell proliferation; and (5) the ability to modulate the development, differentiation, proliferation and/or activity of cells that form blood vessels and coronary tissue, e.g., coronary smooth muscle cells and/or blood vessel endothelial cells.
For INTERCEPT 258, biological activities include, e.g., (1) the ability to modulate protein-protein interactions (e.g., homophilic and/or heterophilic), and protein-ligand interactions, e.g., in receptor-ligand recognition; (2) ability to modulate cell-cell interactions; (3) the ability to modulate the host immune response; (4) the ability to modulate cell proliferation, e.g., gastrointestinal tract epithelial cell proliferation; (5) the ability to modulate intracellular signaling cascades (eg., signal transduction cascades); (6) the ability to modulate pulmonary cell development, differentiation and/or function; and (7) the ability to modulate thrombosis and/or vascularization.
For TANGO 281, biological activities include, e.g., (1) the ability to modulate, e.g., stabilize, promote, inhibit or disrupt protein-protein interactions (e.g., homophilic and/or heterophilic), and protein-ligand interactions, e.g., in receptor-ligand recognition; (2) ability to modulate cell-cell interactions; (3) the ability to modulate the host immune response; (4) the ability to modulate the proliferation, differentiation and/or activity of hematopoeitic cells (e.g. megakaryocytes); (5) the ability to modulate intracellular signaling cascades (e.g., signal transduction cascades) and (6) the ability to modulate platelet function.
In one embodiment, a polypeptide of the invention has an amino acid sequence sufficiently identical to an identified domain of a polypeptide of the invention. As used herein, the term xe2x80x9csufficiently identicalxe2x80x9d refers to a first amino acid or nucleotide sequence which contains a sufficient or minimum number of identical or equivalent (e.g., with a similar side chain) amino acid residues or nucleotides to a second amino acid or nucleotide sequence such that the first and second amino acid or nucleotide sequences have or encode a common structural domain and/or common functional activity. For example, amino acid or nucleotide sequences which contain or encode a common structural domain having about 60% identity, preferably 65% identity, more preferably 75%, 85%, 95%, 98% or more identity are defined herein as sufficiently identical.
In one embodiment, a TANGO 253 protein includes at least one or more of the following domains: a signal sequence, a collagen domain and a C1q domain.
In one embodiment, a TANGO 257 protein includes at least a signal peptide.
In one embodiment, an INTERCEPT 258 includes at least one or more of the following domains: a signal sequence, an extracellular domain, an immunoglobulin (Ig) domain, a transmembrane domain, and an intracellular or cytoplasmic domain.
In one embodiment, a TANGO 281 protein includes at least one or more of the following domains: a signal sequence, an extracellular domain, a photosystem II 10 kD phosphoprotein domain, a transmembrane domain, and an intracellular or cytoplasmic domain.
The polypeptides of the present invention, or biologically active portions thereof, can be operably linked to a heterologous amino acid sequence to form fusion proteins. The invention further features antibodies, such as monoclonal or polyclonal antibodies, that specifically bind a polypeptide of the invention. In addition, the polypeptides of the invention or biologically active portions thereof can be incorporated into pharmaceutical compositions, which optionally include pharmaceutically acceptable carriers.
In another aspect, the present invention provides methods for detecting the presence, activity or expression of a polypeptide of the invention in a biological sample by contacting the biological sample with an agent capable of detecting an indicator of the presence, activity or expression such that the presence activity or expression of a polypeptide of the invention is detected in the biological sample.
In another aspect, the invention provides methods for modulating activity of a polypeptide of the invention comprising contacting a cell with an agent that modulates (inhibits or stimulates) the activity or expression of a polypeptide of the invention such that activity or expression in the cell is modulated. In one embodiment, the agent is an antibody that specifically binds to a polypeptide of the invention.
In another embodiment, the agent modulates expression of a polypeptide of the invention by modulating transcription, splicing, or translation of an mRNA encoding a polypeptide of the invention. In yet another embodiment, the agent is a nucleic acid molecule having a nucleotide sequence that is antisense to the coding strand of an mRNA encoding a polypeptide of the invention.
The present invention also provides methods to treat a subject having a disorder characterized by aberrant activity of a polypeptide of the invention or aberrant expression of a nucleic acid of the invention by administering an agent which is a modulator of the activity of a polypeptide of the invention or a modulator of the expression of a nucleic acid of the invention to the subject. In one embodiment, the modulator is a protein of the invention. In another embodiment, the modulator is a nucleic acid of the invention. In other embodiments, the modulator is a peptide, peptidomimetic, or other small molecule.
The present invention also provides diagnostic assays for identifying the presence or absence of a genetic lesion or mutation characterized by at least one of: (i) aberrant modification or mutation of a gene encoding a polypeptide of the invention, (ii) mis-regulation of a gene encoding a polypeptide of the invention, and (iii) aberrant post-translational modification of the invention wherein a wild-type form of the gene encodes a protein having the activity of the polypeptide of the invention.
In another aspect, the invention provides a method for identifying a compound that binds to or modulates the activity of a polypeptide of the invention. In general, such methods entail measuring a biological activity of the polypeptide in the presence and absence of a test compound and identifying those compounds which alter the activity of the polypeptide.
The invention also features methods for identifying a compound which modulates the expression of a polypeptide or nucleic acid of the invention by measuring the expression of the polypeptide or nucleic acid in the presence and absence of the compound.
Other features and advantages of the invention will be apparent from the following detailed description and claims.